crossing96/oncoscreening huggingface dataset:
CXCL5 promotes mitomycin C resistance in non-muscle invasive bladder cancer by activating EMT and NF-κB pathway.	The emergence of chemoresistance greatly increases the recurrence risk for non-muscle invasive bladder cancer (NMIBC) patients, which is still a big concern of clinicians. Understanding the mechanisms of drug resistance is of great significance for preventing and reversing it. We showed here that CXC motif chemokine ligand 5 (CXCL5) was overexpressed in mitomycin C-resistant bladder cancer cell line M-RT4. Meanwhile, parental RT4 cell treated with recombinant human CXCL5 (rhCXCL5) reduced its sensitivity to mitomycin C. Conversely, knockdown CXCL5 sensitized M-RT4 cell. We further investigated the molecular mechanisms finding that epithelial mesenchymal transition (EMT) and NF-κB pathway were activated in M-RT4 cell, which could be attenuated by knockdown CXCL5. All these data indicated that CXCL5 may promote mitomycin resistance by activating EMT and NF-κB pathway. Thus, our study identifies CXCL5 as a novel chemoresistance-related marker in NMIBC, thereby providing new strategies to overcome chemoresistance for NMIBC patients.	bladder
Effect of a Radical Cystectomy Care Pathway on Postoperative Length of Stay and Outcomes.	OBJECTIVE: To determine whether an enhance recovery protocol for radical cystectomy patient affected the length of stay or the number and type of readmissions that occurred after hospital discharge. MATERIALS AND METHODS: We prospectively assessed 152 cystectomy patients after initiation of the pathway. These patients were compared with the previous 147 patient operated on before the pathway initiation. Eligible patients were those undergoing radical cystectomy with any diversion at our institution. Univariate tests were performed using Wilcoxon sum-rank and chi-square tests. Multivariate analyses were performed using logistic regression models to assess for patient factors related to readmissions. RESULTS: With institution of the pathway, length of stay decreased from 10 to 7.1 days. Our readmission rates did not change significantly. Patients were readmitted for different reasons after pathway implementation, with the rate of urinary tract infection-related readmissions increasing from 14.3% to 40.4%, but with a concomitant decrease in the rate of readmissions for wound and deep space infections from 42.9% to 23.4%. Our venous thromboembolism rate decreased from 6.8% to 3.3% with implementation of the protocol. CONCLUSION: Implementation of a cystectomy care pathway significantly decreased length of stay without an increased rate of readmissions at 30 days. No patient factors predisposed to an increased rate of readmission. Pathway implementation led to a decrease in wound and deep space infection readmissions, but was associated with an increase in urinary tract infection readmissions. Further studies are examining if early intervention can further decrease readmission rates.	bladder
Prehabilitation for major abdominal urologic oncology surgery.	PURPOSE OF REVIEW: Whether prehabilitation in radical cystectomy adds to the effort of reducing postoperative morbidity and impairments in the survivorship phase has until recently received limited attention. This narrative review aims to summarize the current evidence base on prehabilitaion interventions focusing on the efficacy of procedure-specific interventions and the influence on postoperative outcomes. RECENT FINDINGS: Given the oncological risk, there is a relative short window to intervene and proactively optimize the patient before radical cystectomy. Preliminary results are however promising and a single-center randomized controlled trial (RCT) has shown that home-based short-term physical prehabilitation is feasible and effective and significantly improves early mobilization, time to perform activities of daily living and health-related quality of life (HRQoL). No significant impact on length of stay or complications was found. Limited evidence support preoperative nutritional interventions in cancer surgery, although evidence suggests improved outcome if malnourished individuals are adequately fed 7-10 days before surgery. No RCTs have evaluated the effect of smoking or alcohol cessation interventions on complications or HRQoL in radical cystectomy. Patient education interventions focusing on stoma care improve significantly self-efficacy in regards to independently change of stoma-appliance up to 1 year postoperatively. Currently, there is no evidence of early intervention considering psychological well being, sexual health or shared decision-making. SUMMARY: Published data indicate that a group of preoperative multiprofessional interventions including physical exercises, supportive nutritional care and stoma education can postoperatively improve early mobilization, self-efficacy and HRQoL. No evidence for further reduction of length of stay or complications was found.	bladder
Comprehensive genomic profiling of neuroendocrine bladder cancer pinpoints molecular origin and potential therapeutics.	Neuroendocrine bladder cancer is a relatively rare but often lethal malignancy, with cell of origin, oncogenomic architecture and standard treatment poorly defined. Here we performed comprehensive whole-genome and transcriptome sequencing on a unique cohort of genitourinary neuroendocrine neoplasms, mainly small cell carcinomas of the urinary bladder. The mutational landscape and signatures of neuroendocrine bladder cancer strikingly resembled those in conventional urothelial carcinoma, along with typically mixed histologies, supporting a common cellular origin. We identified pervasive age-related and APOBEC-mediated mutagenesis patterns, and one patient displayed a somatic fingerprint attributable to aristolochic acid exposure, an established etiology of urothelial cell carcinoma. Deep RNA sequencing revealed dysregulated tumorigenic pathways and novel fusion transcripts, including a targetable in-frame PVT1-ERBB2 variant associated with aberrant expression of ERBB2 gene (encoding HER2 receptor). Furthermore, we provided preliminary evidence that combined TP53 and RB1 depletion favored lineage switching from oncogene-addicted urothelial cancer cells to neuroendocrine-like tumor cells, and resulted in decreased response to targeted agents. Together, these data present the first high-resolution genomic portrait of neuroendocrine bladder cancer, which holds important implications for the biological understanding and rational treatment of this deadly disease.	bladder
Identification of differentially expressed genes and biological pathways in bladder cancer.	The purpose of the present study was to identify key genes and investigate the related molecular mechanisms of bladder cancer (BC) progression. From the Gene Expression Omnibus database, the gene expression dataset GSE7476 was downloaded, which contained 43 BC samples and 12 normal bladder tissues. GSE7476 was analyzed to screen the differentially expressed genes (DEGs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed for the DEGs using the DAVID database, and a protein‑protein interaction (PPI) network was then constructed using Cytoscape software. The results of the GO analysis showed that the upregulated DEGs were significantly enriched in cell division, nucleoplasm and protein binding, while the downregulated DEGs were significantly enriched in 'extracellular matrix organization', 'proteinaceous extracellular matrix' and 'heparin binding'. The results of the KEGG pathway analysis showed that the upregulated DEGs were significantly enriched in the 'cell cycle', whereas the downregulated DEGs were significantly enriched in 'complement and coagulation cascades'. JUN, cyclin‑dependent kinase 1, FOS, PCNA, TOP2A, CCND1 and CDH1 were found to be hub genes in the PPI network. Sub‑networks revealed that these gene were enriched in significant pathways, including the 'cell cycle' signaling pathway and 'PI3K‑Akt signaling pathway'. In summary, the present study identified DEGs and key target genes in the progression of BC, providing potential molecular targets and diagnostic biomarkers for the treatment of BC.	bladder
Does switching the bacillus Calmette-Guérin strain affect clinical outcome in patients with recurrent non-muscle-invasive bladder cancer after initial bacillus Calmette-Guérin therapy?	PURPOSE: It is still unknown whether switching the bacillus Calmette-Guérin (BCG) strain at the second induction course of BCG therapy has a therapeutic benefit in patients with tumor recurrence after the initial BCG therapy (BCG-relapsing tumor). MATERIALS AND METHODS: We retrospectively reviewed the clinicopathological features of 97 patients treated with a second induction course of BCG therapy between 1986 and 2014. Among the patients initially treated with BCG Tokyo-172, the second course was either BCG Tokyo-172 in 56 (57.8%) or BCG Connaught in 15 (15.5%). Among those who were initially treated with BCG Connaught, the corresponding numbers were 13 (13.4%) or 13 (13.4%), respectively. Twenty-eight (28.9%) patients were given a different BCG strain at the 2 BCG therapies (switching group), and 69 (71.1%) patients were given the same BCG strain (non-switching group). RESULT: The 5-year recurrence-free survival rate of the switching group was 64.7 ± 9.6%, which was not significantly different from that of the non-switching group (54.8 ± 6.9%, P = 0.427). Switching or not switching the BCG strain was not significantly associated with tumor recurrence after the second BCG therapy. The 5-year progression-free survival rate of the switching group was 95.4 ± 2.6%, which was also not significantly different from that of the non-switching group (96.0 ± 3.9%, P = 0.674). Patients treated with BCG Tokyo-172 to Tokyo-172 had significantly higher incidences of side effects during the second BCG therapy. CONCLUSIONS: The results of this study indicate that in patients with a BCG-relapsing tumor after the initial BCG therapy, the same BCG strain as that administered at the initial BCG therapy could be utilized effectively for the second BCG therapy. Patients treated with BCG Tokyo-172 for an initial tumor had a higher incidence of side effects during the second BCG therapy using the same strain.	bladder
Is folic acid safe for non-muscle-invasive bladder cancer patients? An evidence-based cohort study.	BACKGROUND: Patients with cancer are highly concerned about food choices and dietary supplements that may affect their treatment outcomes. Excess folic acid (synthetic folate) from supplements or fortification can lead to accumulation of unmetabolized folic acid in the systemic circulation and urine and may promote cancer growth, especially among those with neoplastic alterations. OBJECTIVE: We investigated the prospective association between synthetic compared with natural folate intake and clinical outcomes in non-muscle-invasive bladder cancer (NMIBC), which is a highly recurrent disease. DESIGN: In a cohort of 619 NMIBC patients, folate intake at diagnosis was assessed with a previously validated food-frequency questionnaire and categorized according to tertiles. After a median follow-up of 5.2 y, 303 tumor recurrence and 108 progression events were documented from medical record review. Multivariable Cox proportional hazards and logistic models were used to estimate adjusted HRs and ORs with 95% CIs. RESULTS: Synthetic folic acid intake was positively associated with a risk of recurrence among NMIBC patients (medium compared with low intake-HR: 1.72; 95% CI: 1.20, 2.48; P = 0.003; high compared with low intake-HR: 1.80; 95% CI: 1.14, 2.84; P = 0.01). Patients with a higher folic acid intake were more likely to have multifocal tumors at diagnosis (medium or high compared with low-OR: 2.08; 95% CI: 1.08, 4.02; P = 0.03). In contrast, natural folate intake tended to be inversely associated with the risk of progression (medium or high compared with low-HR: 0.68; 95% CI: 0.44, 1.04; P = 0.08). CONCLUSIONS: A high intake of synthetic folic acid, in contrast to the natural forms, is associated with an increased risk of recurrence in NMIBC and multifocal tumors at diagnosis, which suggests that folic acid may be unsafe for NMIBC patients. These findings provide some evidence for nutritional consultation with regard to folate intake among NMIBC patients.	bladder
Update on early instillation of chemotherapy after transurethral resection of non-muscle-invasive bladder cancer.	Non-muscle-invasive bladder cancer (NMIBC) is a highly recurrent disease. Early bladder chemotherapy instillation (EBCI) after transurethral resection (TURB) is an efficient way to diminish recurrence. However, this method is often challenged. Areas covered: There was a recent publication of a large meta-analysis with the original patient data and the largest study ever on EBCI. Both brought new evidence on EBCI. Also the results of the 2 trials of EBCI with apaziquone appeared. EBCI is discussed among other methods to decrease recurrence. Expert commentary: EBCI obtains a 35% relative reduction of recurrence with the best results in low risk tumors. However, tumors with an EORTC recurrence score of 5 or more do not respond. It should be given within a few hours after TURB. Mitomycin C and epirubicin have been most widely used with no difference in response. Intensive rinsing of the bladder is also able to reduce recurrence rates by about 21%. A rare, but major problem and reason for not using EBCI is the possible extravasation of the drug after TURB. Apaziquone is rapidly inactivated in tissue and blood and is therefore ideal for local use. Two phase III trials however obtained only a modest result.	bladder
Snail immunohistochemical overexpression correlates to recurrence risk in non-muscle invasive bladder cancer: results from a longitudinal cohort study.	The current WHO/ISUP classification and grading system subdivides urothelial tumours into prognostically distinct categories. Understanding the molecular pathways involved in bladder cancer development can improve patient stratification and management. This study aims to investigate the relationship between Snail, Slug and E-cadherin expressions and clinico-pathological features of non-muscle invasive bladder carcinoma (NMIBC). All patients attending the same urological centre from January to May 2002, who were pathologically diagnosed with NMIBC, were enrolled in this longitudinal cohort study. E-cadherin, Snail and Slug protein expressions were assessed by immunohistochemical analysis and compared with follow-up data. The main outcome measures were recurrence and progression rates. The cohort under investigation included 43 patients (38 men and 5 women, mean age 67.7 ± 10.6 years). High-grade (HG) carcinomas were 20/43, with 10 invasive cases (pT1). Low-grade (LG) carcinomas were 23/43, with no invasive cases (pTa). Among the eight HGpTa cases with recurrence, strong Snail expression was detected in six (75%). Out of the 17 LGpTa patients who experienced recurrence, 12 (70.6%) showed strong positivity for Snail. Among the 10 HGpT1 cases, recurrence was observed in 4, of which, 3 (75%) stained intensely for Snail. The Kaplan-Meier curves showed significantly different recurrence rates for patients with strong or weak Snail reactivity (p = 0.027). E-cadherin and Slug expression did not correlate with any of the parameters considered. On multivariate analysis, Snail expression was recognised as an independent prognostic factor for tumour recurrence (p = 0.003). In our study population, Snail immunohistochemical overexpression proved to be related to tumour recurrence in patients affected by NMIBC.	bladder
T4 urothelial carcinoma in undiagnosed closed bladder exstrophy in a post-menopausal female.	It is rare to see an adult presenting with exstrophy of the bladder. Malignant conversion in exstrophy occurs in 4%, with adenocarcinoma as the most common histopathology. We report the first case of metastatic high grade urothelial carcinoma with squamous and sarcomatoid differentiation arising from undiagnosed, closed bladder exstrophy in a female at advanced age with associated bilateral deep vein thrombosis and clot retention. The patient developed clinical progression of disease despite neoadjuvant gemcitabine-cisplatin and salvage (or palliative) radiotherapy. To the best of our knowledge, this is the first reported case of a primary urothelial malignancy in occult bladder exstrophy.	bladder
Repeat Transurethral Resection in Non-muscle-invasive Bladder Cancer: A Systematic Review.	CONTEXT: Initial treatment for most bladder cancers (BCs) involves transurethral resection (TUR) or tumours. Often more cancer is found after the initial treatment in around half of patients, requiring a second resection. Repeat transurethral resection (reTUR) is recommended for high-risk, non-muscle-invasive bladder cancer (NMIBC) to remove any residual disease and improve cancer outcomes. OBJECTIVE: To systematically review the practice and therapeutic benefit of an early reTUR for high-risk NMIBC. EVIDENCE ACQUISITION: A systematic review of original articles was performed using PubMed/Medline and Web of Science databases in December 2016 (initial) and October 2017 (final). We searched the references of included papers. EVIDENCE SYNTHESIS: We screened 15 209 manuscripts and selected 31 detailing 8409 persons with high-grade Ta and T1BC for inclusion. Detrusor muscle was found at initial TUR histology in 30-100% of cases. Residual tumour at reTUR was found in 17-67% of patients following Ta and in 20-71% following T1 cancer. Most residual tumours (36-86%) were found at the original resection site. Upstaging occurred in 0-8% (Ta to ≥T1) and 0-32% (T1 to ≥T2) of cases. Conflicting data report the impact of reTUR on subsequent recurrence and cancer-specific mortality. Recurrence for Ta was 16% in the reTUR group versus 58% in the non-reTUR group. For T1, recurrence ranged from 18% to 56%, but no clear trend was identified between reTUR and control. No clear relationship between reTUR and progression was found for Ta, although for T1 rates were higher in the non-reTUR group in series with control populations (5/6 studies). Overall mortality was slightly reduced in the reTUR group in two studies with controls (22-30% vs 26-36% [no reTUR]). CONCLUSIONS: Residual tumour is common after TUR for high-risk NMIBC. The reTUR helps in the diagnosis of this residual cancer and may improve outcomes for cancers initially staged as T1. PATIENT SUMMARY: Some bladder cancers (BCs) are aggressive but confined to the bladder surface. Initial treatment includes endoscopic resection. More cancer is found after the initial treatment in approximately half of patients. In the aggressive but confined group of BC, a second resection, a few weeks after the first, may help find this residual cancer and improve outcomes, although the evidence quality for this is weak.	bladder
Application of ERAS (Enhanced Recovery After Surgery) and laparoscopic surgery in the management of patients with bladder cancer.	OBJECTIVE: The enhanced recovery after surgery program (ERAS) has become the base of perioperative management in various surgical specialties. However, limited data are available for radical cystectomy. METHODS: We have analyzed 124 patients undergoing radical cystectomy. For retrospective analysis, the patients were divided into two groups:Group A (n=72) included patients whose surgery was performed before the introduction of the ERAS protocol; and Group B (n=52) included patients who were treated following the items included in the ERAS protocol. The main objective was to assess the length of hospital stay and the permanence in intensive care units (ICU). Other variables were the use of intraoperative blood products, fluid-therapy and medical and surgical complications. RESULTS: Hospital and ICU stay were significantly shorter (p〈0.001) in Group B for patients following the ERAS protocol, which led to reduce 7 hospitalization days and 25.7 hours of overall ICU stay. Regarding fluid replacement following the ERAS protocol, our study showed a statistically significant reduction in the total amount of fluid administered, both crystalloids and colloids, in Group B (p〈0.001). The need of blood transfusion was also lower in Group B with a statistically significant difference (p〈0.001). No statistical differences were observed regarding the incidence of surgical complications. CONCLUSIONS: Introduction of ERAS protocol in radical cystectomy decreases the length of hospital stay, permanence in critical care units, and the need for fluidtherapy and blood product transfusion. However, more and larger studies are needed to prove the efficacy of ERAS for patients undergoing radical cystectomy.	bladder
[Intra- and postoperative complications classified according to the Clavien-Dindo classification in patients > 80 years after transurethral resection of the urinary bladder].	INTRODUCTION:  Urothelial carcinoma of the urinary bladder is a tumour of advanced age. The demographic change increases the number of very old patients ( > 80 years) subjected to TUR-B. MATERIAL AND METHODS:  In a retrospective analysis, perioperative complications in 89 patients (> 80 years), who underwent a transurethral resection of the bladder between 2013 and 2016 in our department, were recorded and evaluated using the Clavien-Dindo grading system. RESULTS: Mean patient age was 87 years (82 - 94). 81 patients (91 %) were treated with oral anticoagulants (32 × ASA, 24 × NOACs, 25 × Marcumar). A histological examination revealed no tumour in 25/89 (28 %) patients, pTa in 28/89 (31 %), pT1 in 22/89 (25 %) and pT2 or higher in 14/89 patients (16 %), respectively. A total of 36/89 (40 %) patients experienced complications according to the Clavien-Dindo classification. 21/89 (23 %) of patients had a prolonged bladder irrigation due to macrohaematuria, 5/89 (6 %) needed surgical reintervention. 14 (12.4 %) patients needed a blood transfusion, 6 (5.3 %) of them preoperatively. According to the Clavien-Dindo classification, 4/89 (4 %) patients were graded as I, 21/89 (24 %) as II, 5/89 (6 %) as IIb and 3/89 (3 %) as IVa, respectively. Three patients (3 %) died postoperatively (Clavien-Dindo V). One of them died as a result of aspiration pneumonia (86 y, ASA IV), one as a result of pulmonary embolism (90 y, ASA IV) and one as a result of multiorgan failure (84 y, ASA III). In multivariate analyses, a tumour stage > T2 was confirmed as a significant predictor of the occurrence of postoperative complications (odds ratio of 9.541 (95 % CI 1.14 - 84.67 p = 0.032). For oral anticoagulants the odds ratio was 4.10 (95 % CI, 41.00 - 1.23, p = 0.050). CONCLUSION: Overall, the data show that a TUR-B is feasible in patients > 80 years with an increased complication rate in comparison to younger patients. Prolonged macrohaematuria and a high transfusion rate are attributable to the high percentage of orally anticoagulated patients.	bladder